Aqueous Bendamustine Cyclodextrin Composition for Liquid Stability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Bendamustine is highly reactive with water, necessitating lyophilization for storage stability, which requires reconstitution and includes organic solvents that burden cancer patients.
Innovation Solution
A pharmaceutical composition comprising bendamustine, sulfobutyl ether beta-cyclodextrin (SBECD), and an aqueous diluent with an SBECD concentration between 40% and 60% (w/w) provides storage stability at refrigerated temperatures without lyophilization, eliminating the need for organic solvents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If bendamustine is lyophilized to achieve storage stability, then stability is improved, but the process requires reconstitution and includes organic solvents that increase patient burden
Solution Approach 1:
SBECD acts as an intermediary substance that forms an inclusion complex with bendamustine, protecting it from degradation while allowing the formulation to remain in liquid form without requiring lyophilization or organic solvents
Solution Approach 2:
The invention changes the concentration parameter of SBECD to between 40-60% w/w in the aqueous solution, which enables the formulation to achieve stability without lyophilization while avoiding organic solvents
2Ease of operation
If bendamustine is formulated as liquid without lyophilization, then ease of administration is improved, but stability deteriorates
Solution Approach 1:
SBECD serves as a protective intermediary that allows bendamustine to remain stable in liquid form without lyophilization, eliminating the need for reconstitution while maintaining stability
Solution Approach 2:
The invention creates a composite aqueous formulation containing bendamustine, SBECD, and aqueous diluent in specific proportions (SBECD 40-60% w/w) that achieves both stability and ease of administration
3Stability of the object's composition
If organic solvents are used in bendamustine formulation, then stability is improved, but patient burden increases due to metabolism requirements
Solution Approach 1:
The invention extracts and eliminates organic solvents from the formulation by using SBECD as a stabilizing agent in an aqueous-based system, removing the harmful metabolic burden while maintaining stability
Solution Approach 2:
SBECD acts as an intermediary that provides stability without requiring organic solvents, allowing the formulation to be based on aqueous diluent only
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The composition maintains desirable stability and allows for rapid administration, reducing patient burden by avoiding lyophilization and organic solvents.
Implementation Method 1
bendamustine in complex form has been shown to be effective against solid tumors
Implementation Method 2
pharmaceutical composition comprising bendamustine, sulfobutyl ether beta-cyclodextrin (SBECD), and an aqueous diluent
Data Source
AI summary
A pharmaceutical composition comprising: (a) bendamustine; (b) sulfobutyl ether beta-cyclodextrin (“SBECD”); (c) optionally, sodium chloride; and (d) aqueous diluent; characterized in that the SBECD concentration is between 40% and 60% (w/w) based upon the combined weight of the SBECD and aqueous diluent. In addition, a kit comprising (a) a vial of such liquid pharmaceutical composition and (b) a stabilizing agent; as well as a method of treating a cancer patient comprising administering to such patient an effective dose of such pharmaceutical composition.